1. Field of the Invention
The present invention relates to methods of increasing expression yield of a protein of interest. The present invention in particular relates to isolated polypeptides and isolated polynucleotides encoding polypeptides of the invention. The invention furthermore relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.
2. Description of the Related Art
The use of recombinant host cells in the expression of heterologous proteins has in recent years greatly simplified the production of large quantities of commercially valuable proteins which otherwise are obtainable only by purification from their native sources. Currently, there is a varied selection of expression systems from which to choose for the production of any given protein, including bacterial and eukaryotic hosts. The selection of an appropriate expression system often depends not only on the ability of the host cell to produce adequate yields of the protein in an active state, but, to a large extent, may also be governed by the intended end use of the protein.
Typically improved yields have been obtained by improving the stability of the protein product by using different protease mutants or increasing the expression by using a strong promoter for controlling the expression or improving the secretion pathway by using the most efficient signal peptides.
Host cells used for heterologous protein expression are known to be in a state of stress since the protein synthsizing machinery will be pushed to the limit (Rutkowski, D. T., and Kaufman, R. J. (2004), “A trip to the ER: coping with stress”, Trends in Cell Biology 14 (1): 20-28). Proteins involved in stress responses could therefore be advantageously manipulated leading to improved yield of protein products.
It is an object of the present invention to provide such polypeptides the expressions of which are induced or increased during stress conditions and provide methods for improving yield by modifying the expression.